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Long-term observation of Alzheimer's disease and related conditions

Alzheimer's Disease Neuroimaging Initiative 4 (ADNI4)

Observational University of Southern California · NCT05617014

This study is testing how Alzheimer's disease and related conditions change over time by looking at different groups of people, including those with normal thinking, mild memory issues, and dementia, to better understand the disease.

Quick facts

Study typeObservational
Enrollment1500 (estimated)
Ages55 Years to 90 Years
SexAll
SponsorUniversity of Southern California Academic / other
Drugs / interventionsAducanumab
Locations55 sites (Birmingham, Alabama and 54 other locations)
Trial IDNCT05617014 on ClinicalTrials.gov

What this trial studies

The Alzheimer's Disease Neuroimaging Initiative 4 (ADNI4) is a multi-center observational study aimed at validating biomarkers for Alzheimer's disease and related cognitive disorders. It will enroll 1,150 participants across three cohorts: cognitively normal individuals, those with mild cognitive impairment, and dementia patients. Participants will undergo a variety of assessments including clinical evaluations, cognitive tests, neuroimaging, and biomarker analysis over a period of up to five years. This study builds on previous ADNI phases to enhance understanding of the disease's progression and characteristics.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 55-90 who are cognitively normal, have mild cognitive impairment, or are diagnosed with dementia.

Not a fit: Patients with significant cognitive impairment or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved diagnostic tools and treatment strategies for Alzheimer's disease and related conditions.

How similar studies have performed: Previous phases of the ADNI have shown success in advancing the understanding of Alzheimer's disease, making this approach a continuation of a proven methodology.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria for Newly Enrolled Participants, CN Cohort:

1. Participant may or may not have a significant subjective memory concern as reported by participant, study partner, or clinician.
2. Normal memory function documented by scoring above demographically-adjusted cutoffs on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):

   1. ≥9 for 16 or more years of education
   2. ≥ 5 for 8-15 years of education
   3. ≥ 3 for 0-7 years of education
   4. Note: cut-offs may be modified over time as the field evolves in this area
3. Mini-Mental State Exam score between 24 and 30 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
4. Clinical Dementia Rating = 0. Memory Box score must be 0.
5. Cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living.
6. Stability of Permitted Medications for 4 weeks. In particular, participants may:

   1. Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 years)
   2. Estrogen replacement therapy is permissible
   3. Gingko biloba is permissible, but discouraged
   4. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening.

Inclusion Criteria for Newly Enrolled Participants, MCI Cohort

1. Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
2. Abnormal memory function documented by scoring within the demographically- adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):

   1. ≤11 for 16 or more years of education
   2. ≤9 for 8-15 years of education
   3. ≤6 for 0-7 years of education.
   4. Note: cut-offs may be modified over time as the field evolves in this area.
3. Mini-Mental State Exam score between 24 and 30 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
4. Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5
5. General cognition and functional performance sufficiently preserved such that a diagnosis of dementia cannot be made by the site physician at the time of the screening visit.
6. Stability of Permitted Medications for 4 weeks. In particular, participants may:

   1. Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
   2. Estrogen replacement therapy is permissible
   3. Gingko biloba is permissible, but discouraged
   4. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
   5. Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
   6. Aducanumab and any other approved treatments for the neurobiology of AD if stable for 24 weeks prior to screen

Inclusion Criteria for Newly Enrolled Participants, DEM Cohort

1. Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
2. Abnormal memory function documented by scoring within the demographically- adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):

   1. ≤11 for 16 or more years of education
   2. ≤9 for 8-15 years of education
   3. ≤6 for 0-7 years of education.
   4. Note: cut-offs may be modified over time as the field evolves in this area.
3. Mini-Mental State Exam score between 20 and 28 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
4. Clinical Dementia Rating = 0.5 or 1.0.
5. Meets the National Institute on Aging/Alzheimer's Association Diagnostic Guidelines for Dementia (2011)
6. Stability of Permitted Medications for 4 weeks. In particular, participants may:

   1. Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
   2. Estrogen replacement therapy is permissible
   3. Gingko biloba is permissible, but discouraged
   4. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
   5. Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
   6. Aducanumab and any other approved treatments for the neurobiology of AD if stable for 24 weeks prior to screen

Inclusion Criteria for Newly Enrolled Participants, All Cohorts

1. Geriatric Depression Scale score less than 10.
2. Age between 55-90 years (inclusive).
3. Study partner who has frequent contact with the participant (i.e., minimum average of 2 hours per week) and may be able to accompany the participant to clinic visits or provide information remotely (e.g. over the phone).
4. Visual and auditory acuity adequate for neuropsychological testing.
5. Good general health with no diseases expected to interfere with the study.
6. Participant is not pregnant, lactating, or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile).
7. Willing and able to participate in a longitudinal imaging study.
8. Must be literate and speak English or Spanish fluently.
9. Agrees to collection of blood for GWAS, APOE testing, DNA and RNA testing
10. Agrees to collection of blood for biomarker testing.
11. The Administrative Core, described in section 9.1.1, will collaborate with leadership from all Cores to review the blood biomarker data from the remote blood cohort and select participants to join the in-clinic cohort. See ADNI4: Remote protocol.
12. Agrees to participate in the ADNI study which includes cognitive evaluation, MRI and PET scans.
13. Flexibility can be made to all criteria for those with at least 8 years in a low socio-economic status (SES) neighborhood.

Inclusion Criteria for Rollover Participants, All Cohorts

The following additional inclusion criteria apply to all diagnostic categories for rollover participants only:

1. Must have been enrolled and followed in one of the following previous ADNI studies: ADNIGO, ADNI2, ADNI3 for at least one year.
2. Willing and able to continue to participant in an ongoing longitudinal study. A reduced battery of tests is allowable.
3. Study partner may be available who has frequent contact with the participant (i.e., minimum average of 2 hours per week), and may be able to accompany the participant to clinic visits or provide information remotely (e.g. over the phone).

Exclusion Criteria for Newly Enrolled Participants, CN Cohort:

1.Any significant neurologic disease, such as Parkinson's disease, vascular cognitive impairment/dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities

Exclusion Criteria for Newly Enrolled Participants, MCI and DEM Cohorts:

1.Any significant neurologic disease other than suspected Alzheimer's disease, such as Parkinson's disease (Parkinsonian symptoms complicating MCI/AD are acceptable), vascular cognitive impairment dementia (multiple lacunes less than or equal to 1.5 cm and/or extensive white matter changes are acceptable), Huntington's disease, normal pressure hydrocephalus, brain tumor (clinically insignificant meningioma acceptable), progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.

Exclusion Criteria for Newly Enrolled Participants, All Cohorts:

Additional exclusion criteria apply to all diagnostic categories for newly enrolled participants:

1. Screening/Baseline MRI brain scan with evidence of infection, or other clinically significant focal lesions. Participants with cortical strokes, not large enough to distort anatomy, multiple lacunar infarctions or extensive white matter disease are allowed.
2. Screening/Baseline MRI brain scan with evidence of large structural abnormalities that would corrupt image analytical pipelines - e.g. large hemispheric infarcts, large areas of encephalomalacia, large arachnoid cysts
3. Unable to complete MRIs for any reason (e.g. pacemaker or other implanted metal devices, severe claustrophobia, anxiety which prevents MRI scans, too large to fit, etc.).
4. Current major depression, bipolar disorder as described in DMS-IV within the past 1 year. Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol.
5. Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder.
6. History of schizophrenia (DSM-5 criteria).
7. History of alcohol or substance disorder within the past 2 years (DSM-5 criteria).
8. Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol.
9. Clinically significant abnormalities in B12, or thyroid function tests that might interfere with the study. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
10. Residence in skilled nursing facility
11. Current use of specific psychoactive medications (e.g. certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.), at the discretion of the clinician.
12. Current use of any other exclusionary medications.
13. Investigational agents are prohibited for five half-lives or one month, whichever time period is longer, prior to entry and for the duration of the trial.
14. Participation in clinical studies involving neuropsychological measures being collected more than once time per year.
15. Female that is pregnant, lactating, or of childbearing potential.
16. Flexibility can be made to all criteria for those with at least 8 years in a low socio-economic status (SES) neighborhood.

Where this trial is running

Birmingham, Alabama and 54 other locations

+5 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Mild Cognitive ImpairmentAlzheimer DiseaseDementiaamyloidplaquesneuroimagingbiomarkerscognition disorder
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.